Scientific program Day 2

Work shop Title: Ebola: Actual situation, and development of a novel preventive vaccine against multiple Ebola virus strains

Biography:

Ahmed Bouzidi is the founder of Vaxeal. Today, Vaxeal is a key player in the field of immuno-oncology. He previously founded and managed SEDAC-Therapeutics inc., a leading biotech pioneer in peptide-based therapeutic vaccines (exit by Leveraged Buy Out), and Biophysiomics inc. (acquired by Chengdu Kuachang Science & Technology, China). He is a board member of Vaccines Europe and of the European Biopharmaceutical Enterprises (EBE-biopharma), and is a Senior Associate of the Royal Society of Medicine. He held previously senior advisory positions with Chinese pharmaceutical companies and public institutions, and worked 10 years as senior researcher at the LFB. He holds a Master degree in Animal Biology (University of Lille, France), a PhD in Cellular Biology, and a MBA in Finance (University of New Hampshire, USA).

Abstract:

Ebola virus (EBOV) is a member of Filoviridae family of viruses, which have been associated with large outbreaks of hemorrhagic fever in human and nonhuman primates with high case fatality. Since 1976, when the virus was first discovered, five Ebola virus species have been isolated, differing by as much as 40% in amino acid sequence: Zaire (ZEBOV), Sudan (SEBOV), Reston (REBOV), Cote d’Ivoire (CIEBOV) and the newly discovered Bundibugyo Ebola virus (BEBOV) 1.All of the viruses in the family except for REBOV are highly pathogenic for humans. The recent Ebola outbreak in West Africa has reached historic proportions and underscores the vulnerability of populations worldwide to pathogens. Outbreaks of Ebola virus disease have occurred in Africa in the past 2, however the current epidemic caused by ZEBOV [Guinea-Zaire ebolavirus H.sapiens-tc/GIN/2014/Gueckedou-C] 3, has been characterized by greater breadth and rapid spread (reported cases and geographically). Currently, there are no vaccines or antiviral drugs approved for prevention or treatment of Ebola infections in humans. However, the severity of the recent Ebola outbreak and failure of the health care system to contain the infection rates in West Africa underscore the need for the rapid development of a safe and effective pan-Ebola vaccine. Such a vaccine, rapidly inducing strong and long-lasting protective immune responses against all main Ebola strains and that can be readily produce and deployed in the field, is needed to protect people in endemic regions in an event of an outbreak but also to protect healthcare workers caring for Ebola patients, who are at the highest risk of infection even before an outbreak can be identified.

A handful of EBOV vaccine candidates are under development, most of them being monovalent vector-based vaccines targeting the ZEBOV glycoprotein (GP). Some of them have been demonstrated to be effective in preclinical trials using small animal and non-human primates (NHP) models, showing that protection against EBOV infection is achievable by vaccination. To date, three main vector-based vaccine candidates have undergone phase 1 clinical trials, demonstrating their safety and immunogenicity, and the preliminary results of a Phase 3 trial for a Vesicular Stomatitis Virus-based vaccine (rVSV-EBOV – Merck Vaccines USA) suggest that this vaccine might be “highly efficacious and safe” in preventing Ebola virus disease 4,5.

However, these 1st generations of Ebola virus vector-based vaccines, primarily developed to fight bioterrorism, are not adapted for large-scale vaccination in Sub-Saharan countries and some major obstacles may limit their human application and their deployment in endemic regions. One significant downside is their need for storage at -80°C to ensure their long-term stability and biological activity. The viral vector constructs may not be safe or effective in producing long-term protection against Ebola. Moreover, pre-existing immunity to the vectors, such as adenoviruses, has been already found to counteract the action of vector-based vaccines and to favour infection. Finally, while most of the T cell responses mounted in Ebola patients have been found to target the nucleoprotein (NP), the Ebola vaccine candidates only focus on the Ebola GP 6. Hence, the challenge lies in producing non-viral vector-based Ebola vaccines, safe and effective, allowing readily deployment in an event of an outbreak and harnessing both specific, strong and long-term humoral immune responses and the right balance of CD4+ and CD8+ T-cell responses, which are both fundamental to protect against the virus.

PEVIA consortium aims to develop a new 2nd generation of vaccines, comprising two complementary and synergistic approaches for the design of safe and effective preventive vaccines against multiple Ebola virus strains, ease to produce and to deploy in the endemic regions. These approaches, based on the Ebola surface glycoprotein and nucleoprotein, include: 1/ Creation of a recombinant native Ebola GP based vaccine to generate robust anti-EBOV neutralizing antibodies and long-term humoral responses, and 2/ Development of a long synthetic peptides (LSP) based vaccine containing multiple overlapping CD4+ and CD8+ T-cell epitopes but also linear and structured B-cell epitopes, all derived from the Ebola GP or NP and highly conserved between all main Ebola strains, to generate specific, multiple, strong and long-lasting cellular responses. The prime-boost combination of the recombinant protein and LSP-based vaccines will focus on the optimization of B and T-cell antigens with the objective to generate both strong B and T-cell memory responses against various EBOV strains. This strategy will improve vaccine efficacy against various strains of a mutating virus to give a long lasting protection against multiple exposures to Ebola virus. In addition, our vaccine will not require storage at low temperatures (+4 to +8°C), overcoming the problems of stability, and storage in endemic regions, and allowing for ready deployment in the field.

The objectives of the PEVIA’s project are: 1/ To manufacture in industrially applicable CHO cells a recombinant Ebola GP variant in its most relevant structure for immunizations in order to determine safety, and the antibody response profile in vitro and in animal models, 2/ To manufacture Long Synthetic Peptides containing CD4+ and CD8+ T-cell epitopes derived from Ebola GP and NP in order to determine safety, humoral and cellular response profile in vitro and in animal models, 3/ To identify the optimal prime-boost vaccination strategies for clinical trials, based on the capacity to induce both strong and long-term cellular and antibody responses against various EBOV strains, 4/ Phase Ia dose-escalation clinical study in Europe of selected vaccine candidates and prime-boost (1 + 2) vaccination strategies to assess their safety and immunological profile, and 5/ Phase Ib clinical trial in endemic region with the most promising formulation.

PEVIA consortium also aims to develop innovative functional analysis tools and in vitro methods to accelerate preclinical and clinical development of EBOV vaccine candidates and to determine correlates of immune protection against Ebola virus disease in humans. This includes: 1) Identification of new relevant EBOV GP and NP derived CD4+ and CD8+ T-cell epitopes for pre-clinical and clinical immune monitoring, 2) Development of innovative in vitrobioassays for characterizing, detecting and quantifying under BSL-2 conditions neutralizing and enhancing antibodies against different subtypes of Ebola and filovirus induce with vaccine candidates (functional analysis), and 3) Validation of relevant chimeric and humanized mouse models for EBOV infection suitable for studies on protection and immunology of vaccine candidates against Ebola virus, or other filovirus, in a ‘human’ or in a murine context.

Arifa Aziz

Aga Khan University Hospital, Pakistan

Audit on incidents and knowledge of nurses about chemotherapy extravasations at a day care oncology in a tertiary care hospital in Karachi, Pakistan

Biography:

Arifa Aziz, working as a staff medical officer and supervisor Day Care Oncology at Aga Khan University Hospital Karachi, Pakistan. Day care oncology is a fifty four bed unit which runs in two shifts and accommodate eighty five to ninety patients daily for chemotherapy administration, blood transfusions, intrathecal chemotherapy bone marrow biopsy and lumbar puncture. She has over nineteen years of experience in adult oncology, written a book by name “Hematology and Oncology Hand Book of Cancer Chemotherapy Protocols” This is a registered book with ISBN;978-969=8073-30-5., is the only chemotherapy protocols book which was written and introduce in Pakistan, first edition was in 2013 and second edition in May 2017. Papers with title “Innovation in chemotherapy administration process” published in Indian journal of cancer and “Incentives of 5 FU infusions through pump and decrease stay in hospital” published in Innovative Journal of Medical and Health Science. Study on quality of life of breast cancer patients receiving first line chemotherapy in a tertiary care hospital accepted for oral presentation and Audit on incidents of chemotherapy extravasations in day care oncology at a tertiary care hospital in Karachi, Pakistan was accepted for poster presentation, at IARMM 6th World Congress of Clinical Safety 2015 in Rome, Italy 6 – 8 September 2017.

Abstract:

Background

Extravasations of cytotoxic agents after its intravenous administration results in a serious damage to the tissues leading to local injury and tissue necrosis. This audit was conducted to assess the knowledge of nursing staff regarding identification and management of chemotherapy extravasations and teaching to the patients, in addition we also recorded number of incidents reported. Audit was conducted at day care oncology of Aga Khan University Hospital.

Method

Core team was formulated for audit and checklist was developed. Check points were initial assessment of intravenous cannulation site, knowledge about extravasations management and teaching of the patients about signs and symptoms of extravasations. Patient’s data was collected from 12th February till 15th June 2016 for incidents of extravasations reported.

Results

Total numbers of twelve nurses were audited; out of twelve, seven nurses (58.33 %) were not observing all the components in terms of proper local examination,assessing areas of last intravenous cannulation site and giving proper teaching to the patient about signs and symptoms of extravasations and has less knowledge about its management. Five (41.67%) out of twelve nurses, have knowledge of extravasations assessment, management and patients teaching. Nursing staffs teaching material on the assessment and management of extravasations was not available at day care oncology. Seven (1.28%) incidents of extravasations were reported during the above said time. Total numbers of Cytotoxic drugs administered during this time were five thousands four hundreds and sixty one (5461).Instituinal bench mark is 0.7/1000.

Conclusion

Extravasation is not very common. However, it was reported to be twice as frequent as compared to institutional made bench mark. Lack of knowledge was reported to be present in >58% of day care nurses.

Way forward

Frequency can be reduced with prevention, prompt identification and early management.Develop educational material and videos on extravasations identification, patients teaching and management for day care oncology nurses. To re-audit process of assessment and management of chemotherapy after 12 months.The second audit was started in August 2017,and is currently in progress.

HidayatUllah

Aga Khan University Hospital, Pakistan

Chemotherapy induced amenorrhea and its perceived psychosocial effects in patients with breast cancer

Biography:

Hidayat Ullah completed his M.B.B.S followed by M.C.P.S in Medicine and about to complete my F.C.P.S in Medical Oncology at the Aga Khan University Hospital Karachi by December this year. He worked in the department as Chief Resident, leading a team of many residents, engaging in various residency and educational activities besides clinical work. He was a coordinator for one of the largest Multidisciplinary tumor board meetings, innovating and enhancing its quality to improve patient care. To improve his knowledge, he did preceptor ship programs with Icon oncologist Prof.Ion Tannock, Professor Emeritus Princess Margaret Hospital Toronto on two occasions and have rotated in one of the other largest cancer institutes of the country, the shoukat khanum memorial Hospital and research center Lahore.

Abstract:

Background:

Breast cancer is the most common cancer affecting women, and the leading cause of cancer death. Over 200,000 women between the ages of 20–49 are diagnosed with cancer every year after definitive local treatment; adjuvant chemotherapy is given in order to prevent recurrence. The chemotherapeutic agents have been known to cause premature amenorrhea often; irreversible. Chemotherapy induced amenorrhea is one of the major adverse outcome which ultimately leads to psychological disturbance among patients with breast cancer. This study was conducted to know the frequency and perceived psychosocial effects of chemotherapy induced amenorrhea in women with breast cancer.

Method:

139 patients with the histologically proven breast cancer who had qualified for receiving chemotherapy during the study period were enrolled on the satisfaction of inclusion and exclusion criteria. Patients demographic details and the breast cancer treatment related information and information regarding the menstrual history were collected through a pre formed questionnaire and the perceived psychosocial impacts / quality of life of the participant were assessed at six months after first contact by using Functional Assessment of Cancer Therapy-Breast (FACT-B) version-4 translated in Urdu language.

Results:

Socio-demographic characteristics of the patients:

A total of 139 patients were included in the study. Mean age of the patients was 41.18 year ± 4.3. Almost 93.5 (130) patients were married having average of 3 children. Ninety-one percent of the married patients had 5 or less children, a major proportion of women belonged to urban areas which constitute 82.7 % of the total.

Majority (85.6 %) of the patients were educated. More than 50 % had education level of higher secondary and above.

Menstrual status of the patients:

About eighty five percent (84.9%) of the patients developed amenorrhea after chemotherapy within six months of the start of chemotherapy

Cycles of chemotherapy:

About 94.2 % of the patients had received three or more than three cycles of chemotherapy with an average duration of chemotherapy of 4.87 months.

Biological markers of the patients:

Majority of patients (92.8%) were either stage II or III of breast cancer at the diagnosis. About 78.4 % were positive for the estrogen and progesterone receptors and 79.1 % were negative for her 2 neu receptor.

Perceived psychosocial effects:

With regards to the psychosocial effect of chemotherapy induced amenorrhea 87 % of the patients had a moderate quality of life, 10 % of the patients had high while 2.2 % of the patients had a low quality of life.

Conclusion:

It is concluded in our study the about 85 percent of the patient have had chemotherapy induced amenorrhea, while about78 percent of the patient had a moderate quality of life.

Biography:

Zarka Samoon has completed her M.B.B.S, followed by MRCP in medicine. She completed her Medical Oncology fellowship at Aga Khan University Hospital. She passed both MRCP certificate exam and FCPS in Medical Oncology. She is a Medical Oncology faculty at Aga Khan University Hospital with keen interest in breast and female genital tract malignancies. She has published an e-book chapter ‘Chemotherapy and targeted agents in triple negative breast cancer’ in Avid Science. Her scientific paper titled ‘Applying Multinational Association of Supportive Care of Cancer Index Score for Identifying Febrile Neutropenia Patients at High Risk of Complications at Tertiary Care Hospital, Pakistan..’ has been published in Open Journal of Epidemiology. She is at present involved in multiple research projects which are in various stages of completion. She is Medical Oncology residency program coordinator and actively involved in teaching undergraduates and postgraduates. In her free time she enjoys reading, blogging and cooking.

Abstract:

Introduction

Metaplastic breast carcinoma (MBC) is a rare disease with an incidence of <1%. In comparison to invasive ductal carcinomas (IDC), MBC present with a larger tumor size, few nodes involved, mostly high grade and triple negative, and with a shorter overall survival.

Objectives

To determine the progression free, and overall survival of patients with MBC.

Methods

From July 2006 till June 2013, 42 patients with MBC treated at Aga Khan University Hospital, Karachi were identified and retrospectively reviewed. Kaplan-Meier method was used for survival analysis.

Results

Prevalence of MBC was 1.92% among breast cancer patients. The median age at tumor diagnosis was 54 years. Thirty nine (92.9%) patients had grade III tumor. The most common histopathology was squamous (69%) followed by spindle (9.5%) and carcinosarcoma (7.1%). Median tumor size was 4.7 cm. Nineteen (45.3%) patients had nodal involvement. Five patients (11.9%) had metastatic disease at presentation. Hormone receptors were positive in 19 (45.2%) patients and negative in 16 (38.1%) patients. Her-2 neu receptor was positive in 9 (19%) patients. Twenty seven (64.3%) patients underwent modified radical mastectomy. Neoadjuvant and adjuvant chemotherapy (anthracycline based in most cases) was received by 10 (23.8%) and 19 (45.2%) patients respectively. Both the median progression free and overall survival was 38 months. Five year progression free and overall survival was 79.5% and 78.9% respectively.

Conclusion

Our patients had tumors which were mostly high grade, large, with around half of them having nodal and hormonal involvement however with better survival outcomes compared to series described earlier.

Biography:

Will be added shortly

Abstract:

Multinational Association of Supportive Care of Cancer (MASCC) index score is a clinical tool to predict outcomes in febrile neutropenia patients. This risk-index score has been authenticated in international trials however local data is deficient. We aimed to determine hospital based incidence rate of serious complications in admitted chemotherapy induced febrile neutropenia patients presenting to a tertiary care hospital. We also aimed to compare proportions of serious medical complications in patients having MASCC score <21 or ≥21. A hospital based prospective close cohort study was designed and conducted at Oncology wards of The Aga Khan University from February to August 2014. Total of 88 patients, aged 16 and above, with chemotherapy induced febrile neutropenia were identified and divided on the basis of MASCC Score into low or high risk {exposure} groups. Follow up was done from day of admission (day zero) to discharge. Outcome was assessed in terms of development of serious complications. Hospital based incidence rate was estimated. The associations between outcome and qualitative variables were evaluated by using Pearson Chi-square and Fisher’s exact test.

Hospital based incidence rate of febrile neutropenia admission was 5.98%, 95%CI [4.88% - 7.08%]. Out of 88 patients with chemotherapy induced febrile neutropenia 85.2% patients were in the high risk group and 14.8% in the low risk group. Serious complications were found in 21.33% and no patients in high and low risk group respectively. Age > 60 (p = 0.039), MASCC score < 15 (p = 0.002) and an albumin < 2.5 mg/dl (p = 0.046) was associated with higher chance of developing serious complications. Sensitivity, specificity, positive and negative predictive value of MASCC score in predicting risk of serious complications was 21.33%, 100%, 100% and 18.06% respectively. MASCC risk-index score is a useful tool to identify patients at low risk of complications. Hospital based incidence rate of serious complications was 18.2%.

Naseef PP

Jamia Salafiya Pharmacy College, India

Tackling the barriers against Measles Rubella Vaccination in Kerala

Biography:

NASEEF PP is working as an Associate Professor in Jamia Salafiya Pharmacy College. He pursued graduation and post graduation from Calicut University in Pharmacy and completed the PhD open defense under The Tamil Nadu Dr MGR Medical University Chennai. He has 8.5 years of teaching experience. NASEEF is the resource person for Kerala State Pharmacy Council for teaching the working Pharmacist. He has conducted public health and vaccination campaigns. NASEEF has 12 national and international publications and presented papers in various national and international seminars.

Abstract:

Measles is a highly infectious disease and may cause death. It kills nearly 40,000 children every year in India. Rubella may cause birth defects like blindness, deafness, heart defects, mental retardation, liver disorders etc. Government of India has launched a campaign to immunize all children from 9 months up to 15 years of age group with one dose of MR vaccine. Kerala state start MR vaccination campaign in October as a part of national immunization programme.

Addressing the drivers of vaccine hesitancy and the barriers to vaccine acceptance is a complex but important task. While the percentage of hesitant does vary from country to country and in time few, if any, countries are ever free from this problem. Overcoming hesitancy requires detection, diagnosis and tailored intervention as there is no simple strategy that can address all of the barriers to vaccine acceptance. Immunization program managers and health care workers need to become adept at recognizing and tackling hesitancy in all of its incarnations if high levels of vaccine acceptance are to be achieved but must also actively support immunization acceptors in order to build and support vaccine acceptance resiliency.

The vaccination campaign in Kerala include contributions from Government and NGOs. The government conducted awareness classes in schools, worship centers, home visit, announcement vehicle etc. the Non Government Organizations conducted public health meets, women empowerment programme etc. the representatives of UNICEF arranged meeting with the community leaders and media representatives and assured their whole hearted support for the campaign.

Vaccination against Measles and Rubella was perceived as more important than other vaccines, and Government subsidy was regarded as an important public health strategy. The most significant barriers to prescribe MR vaccines consisted of parental refusal due to safety concerns. Public health education on safety and efficacy of vaccination is done, and support by Governmental funding would be an important factor to enhance vaccination rates.